Lilly goes with the flow

Lilly joins the continuous manufacturing bandwagon with a CGMP process.

In line with FDA’s push for companies to shift from batch processing to continuous manufacturing, Eli Lilly and Co. has published details of the first CGMP process for an API. The system shrinks a multi-room footprint to equipment that fits in a fume-hood, supporting flexible, small volume production of clinical compounds.

The company believes the approach has far-reaching applications, from expanding possibilities in research to supporting programs for rare diseases and fueling the rise of personalized medicine.

On June 16, Lilly scientists published in Science the rationale and steps involved in continuous manufacturing of prexasertib monolactate monohydrate, a CHK1 and CHK2 inhibitor in Phase II testing for head and neck and other cancers.

The goal of continuous manufacturing is to provide a seamless process that avoids the discrete steps and often lengthy reagent transfer processes that make batch production time consuming and inefficient (see “Practicing Continuity).

Figure: Practicing continuity

The Novartis-MIT Center for Continuous Manufacturing has pioneered an end-to-end process for continuous manufacturing of drugs manufacture. In its system, production steps spanning API synthesis, filtration, crystallization, drying and tablet formation are engineered to flow together -- in contrast to conventional, large-scale batch methods of production, where the steps are discrete. Continuous manufacturing reduces the scale and time of CMC, by enabling continuous sampling of intermediate steps to ensure quality control across the entire process.

The figure depicts a continuous manufacturing process that links multiple steps in an unbroken chain: the introduction of chemical substrates (B1 and B2); addition of reagents such as N2 and SOCL2, intermediates (B4), solvent and excipient at the appropriate stages; removal of byproducts, such as SO2 and HCl, and excess solvent; air in and air out to dry the product; and the release

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